HIF-1α过表达肿瘤抗原在树突状细胞活化及强效抗肿瘤免疫应答中的探索性研究

Tumor-specific antigens play an important role in dendritic cell (DC)-based immunotherapy. The acquisition of tumor-specific antigens, which are essential for DC-based immunotherapy, poses a significant challenge. This study aimed to explore the efficacy of hypoxia inducible factor-1α (HIF-1α) overexpression tumor antigens in DC-based immunotherapy.

An HIF-1α over-expression cell line was constructed to prepare HIF-1α overexpression tumor antigens. The expression of CD14, CD40, CD80, CD86, and HLA-DR on the surface of dendritic cells derived from monocytes was assessed using flow cytometry after stimulation with tumor antigens enriched in HIF-1α. T cell proliferation was analyzed by CFSE division following incubation with mature DCs. The apoptotic tumor cells were detected through annexin V/PI staining following coculture with dendritic cells (DCs) stimulated by HIF-1α enriched antigens. The detection of damage-associated molecular pattern molecules (DAMPs) HMGB1 and calreticulin (CALR) was performed using Western blotting.

The results demonstrated that HIF-1α-enriched tumor antigens significantly upregulated the expression of CD40, CD80, CD86, and HLA-DR in DCs compared to normal tumor antigens. Furthermore, co-incubation with HIF-1α-enriched tumor antigen-activated DCs enhanced T cell proliferation and stimulated the T cell-mediated cytotoxicity. Notably, the expression of DAMPs, such as HMGB1 and CALR, was elevated in HIF-1α-enriched tumor antigens.

Our findings demonstrate that tumor antigens enriched with HIF-1α may encompass tumor-specific antigens capable of stimulating DC activation, thereby enhancing T cell proliferation and cytotoxicity. These results provide support for the further advancement of HIF-1α enriched tumor antigens in preclinical and clinical investigations pertaining to tumor treatment.